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Biomedical subjects

D Hanna

Publications and source records attributed to D Hanna.

At least 19 recordsLinked to original sources

Developing and implementing new safe practices: voluntary adoption through statewide collaboratives.

BACKGROUND: Disseminating new safe practices has proved challenging. In a statewide initiative we developed a framework for (1) selecting two safe practices, (2) developing operational details of implementation, (3) enlisting hospitals to participate, and (4) facilitating implementation. METHODS: Potential topics were selected by a multistep process to identify candidate practices, review the evidence for efficacy and feasibility, and then select them on the basis of importance, efficacy, feasibility, and impact. A multi-stakeholder advisory group representing all constituencies selected two practices: reconciling medications (RM) and communicating critical test results (CTR). Operational details and strategies for implementation were then developed for each practice using a consensus process of discipline stakeholders led by content experts. Hospital CEOs were solicited to participate by the Massachusetts Hospital Association which made the project a "flagship" initiative. A collaborative model was used to facilitate implementation, following the IHI Model for Improvement. In addition to providing exposure to content and method experts, we gave teams a "toolkit" containing recommendations, a change package, and implementation strategies. Each collaborative met four times over an 18 month period. Results were assessed using the IHI team assessment scale and surveys of teams and hospital leaders. RESULTS: Hospital participation rate was high with 88% of hospitals participating in one or both collaboratives. Partial implementation of the practices was achieved by 50% of RM teams and 65% of CTR teams. Full implementation was achieved by 20% of teams for each. CONCLUSIONS: Major factors leading to hospital participation included the intrinsic appeal of the practices, access to experts, and the availability of implementation strategies. Team success was correlated with active engagement of a senior administrator, engagement of physicians, increased use of PDSA cycles, and attendance at collaborative meetings. The prior development of subpractices, recommendations and implementation strategies was essential for the hospital teams. These should be well worked out before hospitals are required to implement any guideline.

Communication↗

Evaluation of the needs of spouses of female carriers of mutations in BRCA1 and BRCA2.

The process of genetic testing involves the entire family, including spouses. The objective of this study was to measure the specific needs and to describe the experiences of spouses of women who received genetic counseling for a positive BRCA1/2 result. We surveyed 59 spouses of female mutation carriers. The mean length of relationships was 26 years (range: 2.5-50 years). All were supportive of their spouses' decision to undergo genetic testing and counselling. Four respondents stated that they wished that they had received additional support at the time of test disclosure and 20% felt that their wives had received inadequate support. One-quarter of the spouses believed that their relationship had changed because of genetic testing; most felt that they had become closer to their wives. Husbands were most concerned about the risk of their wife dying of cancer (43%), followed by the risk of their spouse developing cancer (19%) and the risk that their children would test positive for the BRCA mutation (14%). Distress levels, measured by the Impact of Event scale, suggest that few spouses were experiencing clinical levels of distress.

Adult↗

Review of preorthotic biomechanical considerations.

The application of an ankle-foot orthosis in poststroke hemiplegia can improve the mechanics of ambulation and functional gait. However, prior to the fitting of an orthotic, the clinician should perform a thorough assessment of the biomechanical elements contributing to mobility problems within the patient. Many of these problems such as joint contracture or weakness should be addressed through physical therapy interventions prior to orthotic prescription. This article reviews the common biomechanical elements that contribute to mobility and gait disability in patients with stroke with special attention to orthotic management.

Journal Article↗

Factors modulating cytosolic calcium. Role in lipid metabolism and cardiovascular morbidity and mortality in peritoneal dialysis patients.

Studies in the uremic rat indicate that insulin resistance and glucose intolerance leading to dyslipidemia are associated with a hyperparathyroid-induced increase in cytosolic calcium ([Ca++i]). These alterations are reversed with verapamil, but recur after discontinuation of the drug, suggesting that increased [Ca++i] is responsible for the metabolic derangement. To our knowledge, no similar studies have been conducted in humans. We retrospectively examined, over 12-year period, the effects of factors that lower [Ca++i] on total serum cholesterol and triglycerides in 176 peritoneal dialysis (PD) patients. Because the study was retrospective, detailed lipid profiles were not available. We therefore relied on the morbidity and mortality outcome related to atherosclerotic vascular disease. Diabetic patients were excluded from the study, because their dyslipidemia and vascular disease are mediated via a different mechanism. The patients were classified into four groups. Group I [high parathyroid hormone (PTH) in the absence of calcium channel blockers (CCBs), n = 56] represented the highest [Ca++i]. Group II (high PTH in the presence of CCBs, n = 43) and group III (lower PTH in the absence of CCBs, n = 37) represented intermediate [Ca++i]. Group IV (lower PTH in the presence of CCBs, n = 40) represented the lowest [Ca++i]. High PTH was defined as > or = 3.0 times normal; lower PTH, as < 3.0 times normal. Lower [Ca++i] was achieved through the use of CCBs, or through lower PTH, or both. Lower PTH was achieved by parathyroidectomy or calcitriol administration. The four groups showed no differences in age, sex, race, weight, dialysis duration, or primary disease. Group I showed a mean serum cholesterol of 358 +/- 27 mg/dL and serum triglycerides of 469 +/- 41 mg/dL. Group II showed mean serum cholesterol of 198 +/- 21 mg/dL and serum triglycerides of 147 +/- 17 mg/dL. Group III showed a mean serum cholesterol of 205 +/- 20 mg/dL and serum triglycerides of 174 +/- 16 mg/dL. Group IV showed mean serum cholesterol of 184 +/- 10 mg/dL (p = 0.008) and serum triglycerides of 103 +/- 8 mg/dL (p = 0.005). The cardiovascular morbidity and mortality incidences were: group I, 64%; group II, 27%; group III, 31%; and group IV, 20% (p = 0.002). We conclude that, in non diabetic PD patients, dyslipidemia is related to a hyperparathyroid-induced increase in cytosolic calcium [Ca++i]. Lowering [Ca++i] by decreasing the parathormone level (via parathyroidectomy or calcitriol administration), or by blocking calcium entry into cells (via CCBs), or both, is associated with less dyslipidemia and improved long-term morbidity and mortality related to atherosclerotic vascular disease.

Arteriosclerosis↗

Evaluation of the needs of male carriers of mutations in BRCA1 or BRCA2 who have undergone genetic counseling.

To date, the concerns of men at risk of inheriting a BRCA1 mutation or a BRCA2 mutation have received little attention. It had been anticipated that few men would be interested in predictive testing when a BRCA mutation was identified in their family. However, these men are often affected emotionally by diagnoses of breast cancer in their relatives and may themselves harbor fears that cancer will develop. Male carriers of BRCA1/2 mutations are at increased risk of development of cancers of several types, including those of the breast and prostate. We conducted an evaluation of the needs and experiences of 59 male carriers of BRCA1/2 mutations followed at either the University of Toronto or Creighton University. We assessed their motivations for seeking genetic counseling and testing, involvement in family discussions of breast and ovarian cancer, risk perception, changes in cancer-screening practices, and overall satisfaction with the genetic-counseling process. The principal motivation for seeking genetic counseling was concern for their daughters. The majority (88%) of men participated in family conversations about breast and ovarian cancer, and 47% participated in conversations about prophylactic surgery. Most men believed that they were at increased risk of development of cancer (prostate, breast, colorectal, and skin cancers). However, fewer than one-half (43%) of the men with no previous diagnosis of cancer stated that their prostate cancer-surveillance practices had changed after they had received genetic test results. More than one-half (55%) had intrusive thoughts about their cancer risk. Although levels of satisfaction were high, practitioners should be aware of (a) potential pressures influencing men to request predictive testing, (b) the difficulties that men encounter in establishing surveillance regimens for breast and prostate cancer, and (c) the general lack of information about men's particular experiences in the medical community.

Adult↗

Detection of prosthetic hip infection at revision arthroplasty by immunofluorescence microscopy and PCR amplification of the bacterial 16S rRNA gene.

In this study the detection rates of bacterial infection of hip prostheses by culture and nonculture methods were compared for 120 patients with total hip revision surgery. By use of strict anaerobic bacteriological practice during the processing of samples and without enrichment, the incidence of infection by culture of material dislodged from retrieved prostheses after ultrasonication (sonicate) was 22%. Bacteria were observed by immunofluorescence microscopy in 63% of sonicate samples with a monoclonal antibody specific for Propionibacterium acnes and polyclonal antiserum specific for Staphylococcus spp. The bacteria were present either as single cells or in aggregates of up to 300 bacterial cells. These aggregates were not observed without sonication to dislodge the biofilm. Bacteria were observed in all of the culture-positive samples, and in some cases in which only one type of bacterium was identified by culture, both coccoid and coryneform bacteria were observed by immunofluorescence microscopy. Bacteria from skin-flake contamination were readily distinguishable from infecting bacteria by immunofluorescence microscopy. Examination of skin scrapings did not reveal large aggregates of bacteria but did reveal skin cells. These were not observed in the sonicates. Bacterial DNA was detected in 72% of sonicate samples by PCR amplification of a region of the bacterial 16S rRNA gene with universal primers. All of the culture-positive samples were also positive for bacterial DNA. Evidence of high-level infiltration either of neutrophils or of lymphocytes or macrophages into associated tissue was observed in 73% of patients. Our results indicate that the incidence of prosthetic joint infection is grossly underestimated by current culture detection methods. It is therefore imperative that current clinical practice with regard to the detection and subsequent treatment of prosthetic joint infection be reassessed in the light of these results.

Animals↗

Immunoradiometric assay for intact human osteocalcin(1-49) without cross-reactivity to breakdown products.

BACKGROUND: Osteocalcin (Oc), a serum marker of bone turnover, circulates in several forms. We developed an assay for intact human Oc and investigated its clinical features. METHODS: We generated goat antibodies and N- and C-terminal Oc. The former was used on solid phase (polystyrene beads), and the latter was used as the tracer in an IRMA. RESULTS: The assay was linear with no cross-reactivity to Oc(1-43), total imprecision (CV) of <10%, and recovery of 100% +/- 10%. Assay values for intact Oc in EDTA plasma samples were unchanged at 18-25 degrees C for 6 h. Values for intact Oc in serum, EDTA plasma, and heparin plasma samples did not change after storage on ice for 8 h. Serum samples from patients with various conditions were stored at -70 or -135 degrees C for up to 5 years and yielded z-scores comparable to an Oc(1-43) IRMA for all conditions except for renal failure. In renal failure, the Oc(1-43) assay values were increased, whereas the intact assay values were in the reference interval. CONCLUSION: Decreases in Oc assay values are inhibited by calcium chelation, and slowed by reduced temperatures. The described assay for intact Oc allows improved specificity for bone compared with an assay for Oc(1-43).

Adolescent↗

Improved detection of infection in hip replacements. A currently underestimated problem.

Our aim was to determine if the detection rate of infection of total hip replacements could be improved by examining the removed prostheses. Immediate transfer of prostheses to an anaerobic atmosphere, followed by mild ultrasonication to dislodge adherent bacteria, resulted in the culture of quantifiable numbers of bacteria, from 26 of the 120 implants examined. The same bacterial species were cultured by routine microbiological techniques from only five corresponding tissue samples. Tissue removed from 18 of the culture-positive implants was suitable for quantitative tissue pathology and inflammatory cells were present in all samples. Furthermore, inflammatory cells were present in 87% of tissue samples taken from patients whose implants were culture-negative. This suggests that these implants may have been infected by bacteria which were not isolated by the techniques of culture used. The increased detection of bacteria from prostheses by culture has improved postoperative antibiotic therapy and should reduce the need for further revision.

Acetabulum↗

Casein kinase II copurifies with yeast DNA topoisomerase II and re-activates the dephosphorylated enzyme.

Mitotic division in yeast requires the activity of topoisomerase II, a DNA topology modifying enzyme that is able to disentangle sister chromatids after DNA replication. Previous work has shown that topoisomerase II is a phosphoprotein in intact yeast cells. We show here that when dephosphorylated in vitro, topoisomerase II is unable to cleave or decatenate kinetoplast DNA. An efficient kinase activity that modifies topoisomerase II on seven major sites was found to copurify with the enzyme purified from yeast. Characterization of this kinase, analysis of phosphotryptic peptides, and studies with a yeast mutant deficient in casein kinase II, indicate that the copurifying kinase is casein kinase II (CKII). Topoisomerase II itself has no self-phosphorylating activity. Modification of topoisomerase II by the copurifying kinase is sufficient to restore decatenation activity after dephosphorylation by alkaline phosphatase. The CKII target sites have been mapped to multiple serine and threonine residues on 4 tryptic fragments within the C-terminal 350 amino acids of yeast topoisomerase II. These results are consistent with a model in which the C-terminal domain of topoisomerase II is a negative regulatory domain that is neutralized by phosphorylation.

Amino Acid Sequence↗

Neutrophil (PMN) phagocytosis and chemotaxis after reperfusion injury.

Neutrophils (PMN) have been implicated as mediators of the reperfusion injury which occurs in skeletal muscle after ischemia. This study was performed to measure PMN phagocytosis and chemotaxis after 3 hr of ischemia followed by 1 hr of reperfusion in a model where a significant reperfusion injury occurred. Baseline blood samples were drawn from an ear artery from New Zealand white rabbits for PMN and serum. The right iliac and femoral arteries were clamped for 3 hr which resulted in a severe clinical reperfusion injury. Just prior to clamp release, blood was harvested from the right iliac vein. After 1 hr of reperfusion, blood was again harvested from the right iliac vein. Phagocytosis was measured by the percentage ingestion of zymosan beads by the PMN. The zymosan beads had been opsonized with baseline (b), ischemia (i), or reperfusion (r) serum. Results for phagocytosis revealed no difference for (b) PMN when opsonized by (b), (i), or (r) serum. A significant increase was seen in (i) PMN phagocytosis when (i) or (r) serum was present. Also, a significant increase in (r) PMN phagocytosis was seen when (i) serum was present (ANOVA: F = 14.47; P = 0.0002). Chemotaxis was evaluated by the number of PMN migrating across a filter. Serum obtained from (b), (i), and (r) blood samples served as the chemoattractants. Significant increases in chemotaxis were observed for (b), (i), and (r) PMN when (i) serum was used as the chemoattractant (ANOVA: F = 7.11; P = 0.0025). We conclude: (1) Rabbit PMN harvested after ischemia and reperfusion demonstrated increased phagocytosis when (i) serum was present.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Improved prognosis for asymptomatic carotid stenosis with prophylactic carotid endarterectomy.

BACKGROUND AND PURPOSE: The value of carotid endarterectomy in asymptomatic patients with high-grade stenosis is controversial. The objective of this study is to compare the immediate and long-term outcome of patients after carotid endarterectomy for asymptomatic carotid stenosis (greater than 75%) with the reported natural history of patients followed nonoperatively to determine whether carotid endarterectomy reduces the subsequent neurological event rate. METHODS: The data from 141 carotid endarterectomies performed in 123 patients between January 1980 and December 1986 were reviewed from the perspective of perioperative results and long-term follow-up to January 1990, providing a follow-up ranging from 3 to 10 years. The mean follow-up was 56.6 months (range 27-117 months). RESULTS: There were no perioperative deaths. There were two postoperative stokes: one in the cerebellar distribution and one in the middle cerebral distribution. During the course of follow-up, no patient suffered a stroke in the hemisphere ipsilateral to carotid endarterectomy. One patient developed ipsilateral transient ischemic attacks 24 months after surgery associated with carotid restenosis. A total of three patients developed four recurrent carotid stenoses, for an incidence of 2.8%. All four recurrences were corrected surgically. CONCLUSIONS: These findings are in marked contrast to the reported natural history of patients with greater than 75% stenosis in which the 1-year neurological event rate is 18% and the 1-year stroke rate is 5%. Although final proof of efficacy for prophylactic carotid endarterectomy in asymptomatic patients will await the outcome of randomized trials, until these data are available, prophylactic carotid endarterectomy is justified in centers of excellence that can perform the surgery with low perioperative risk.

Adult↗

Analgesic effect of intraarticular bupivacaine or morphine after arthroscopic knee surgery: a randomized, prospective, double-blind study.

The effect of 20 mL of intraarticular bupivacaine (0.25%, with or without 1:200,000 epinephrine), morphine (0.03%, with or without 1:200,000 epinephrine), or normal saline on postoperative analgesia after arthroscopic knee surgery was studied in a randomized, prospective, double-blind trial in ASA I-III outpatients receiving general anesthesia (n = 112) or regional anesthesia (n = 27 [spinal (n = 25) or epidural (n = 2)]). The visual analogue pain scores in the postanesthesia care unit and 3, 6, 12, and 24 h after surgery, time to first analgesic use, and total 24-h analgesic requirements were recorded. In those who received general anesthesia, the visual analogue scores were significantly lower in the bupivacaine group compared with both the morphine- and placebo-treated patients (P less than 0.05). The time to first analgesic use was longer in both the bupivacaine and morphine groups when compared with the control group (P less than 0.05). No significant differences were detected in total 24-h analgesic requirements among the groups. Patients who had received regional anesthesia had lower visual analogue scores compared with patients who had received general anesthesia irrespective of the intraarticular treatment (P less than 0.05). Our results indicate that intraarticular injection of bupivacaine after arthroscopic knee surgery provides prolonged analgesia but that there is no significant prolonged analgesia provided by intraarticular morphine.

Adult↗

Superoxide anion release (O2-) after ischemia and reperfusion.

Neutrophils have been implicated as mediators of the reperfusion injury following ischemia. In order to measure neutrophil activation, O2- was determined after 2 hr of ischemia followed by 1 hr of reperfusion (no clinical reperfusion injury) and 3 hr of ischemia followed by 1 hr of reperfusion (significant clinical reperfusion injury). Using New Zealand white rabbits, baseline blood samples were drawn from an ear artery. The right iliac and femoral arteries were exposed and clamped. Just prior to clamp release, blood was obtained from the right iliac vein (ischemia). After 1 hr of reperfusion, blood was again taken from the right iliac vein (reperfusion). Neutrophils were isolated from the blood samples. O2- was determined by the reduction of cytochrome c using a spectrophotometer. In the 2-hr group, results (expressed as mumole O2-/min/2 x 10(6) cells) were: baseline, 0.337 +/- 0.025; ischemia, 0.512 +/- 0.039;* and reperfusion, 0.634 +/- 0.064*. (*P less than .05 as compared to baseline). In the 3-hr group, results were: baseline, 0.391 +/- 0.038; ischemia, 0.413 +/- 0.051; and reperfusion, 0.258 +/- 0.043** (**P less than 0.05 as compared to 2 hr reperfusion). A significant increase in O2- was seen after 2 hr of ischemia followed by 1 hr of reperfusion. However, little O2- increase was seen after 3 hr of ischemia and a significant O2- decrease was seen after 1 hr of reperfusion. We conclude: (1) Neutrophil O2- is stimulated early in ischemia followed by reperfusion; (2) after reperfusion injury occurs (3 hr), neutrophils have been activated and O2- can no longer be stimulated; and (3) O2- in this model may be involved in the clinical reperfusion injury seen.

Animals↗

Neutrophil (PMN) phagocytosis and chemotaxis after 2 hr of ischemia.

The role of PMN in the reperfusion injury after ischemia is unclear. It was the purpose of this study to determine if PMN functions of phagocytosis and chemotaxis were altered after a brief period of ischemia (2 hr) followed by reperfusion (1 hr) in a model where no significant reperfusion injury occurred. Baseline blood samples were drawn from an ear artery from New Zealand white rabbits for PMN and serum. The right iliac and femoral arteries were clamped for 2 hr. Just prior to clamp release, blood was harvested from the right iliac vein. After 1 hr of reperfusion, blood was again harvested from the right iliac vein. Phagocytosis was measured by the percentage ingestion of zymosan by PMN. The zymosan beads had been opsonized wtih baseline (b) (b), ischemia (i), or reperfusion (r) serum. Chemotaxis was evaluated by the number of PMN migrating across a filter. Serum obtained from b, i, and r blood samples served as the chemoattractants. Results for phagocytosis demonstrated a significant increase in i and r PMN as compared to b PMN. Opsonization by b,i, or r serum did not enhance this effect (ANOVA, F = 4.477; P = 0.0266). Similar increases in chemotaxis were observed for i and r PMN which also were not enhanced by the chemoattractants of b, i, or r serum (ANOVA, F = 25.43; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗